IMIPRAMINE INHIBITS SOLUBLE ENKEPHALIN-DEGRADING AMINOPEPTIDASE ACTIVITY IN-VITRO

Considerable evidence has appeared recently connecting the mechanism o f action of some antidepressant drugs with the inhibition of the enzym es responsible for enkephalin degradation. Imipramine in vitro inhibit s the enkephalin-degrading aminopeptidase MII and interacts with the e nzyme in a mixed competitive-noncompetitive manner. The present work s hows that imipramine in vitro also inhibits reversibly soluble enkepha lin-degrading aminopeptidase activity in rat brain. Kinetic analysis s howed that this enzyme has two different binding sites for the drug, a nd that imipramine interacts with the enzyme in a mixed noncompetitive -acompetitive way. (C) 1998 Elsevier Science B.V. All rights reserved.